SUMMARY ? CORE A The four research projects of the Program Project propose laboratory characterization of the consequences of genetic variation for carcinogenesis and cancer therapy. These studies are focused on genes involved in Base Excision Repair (BER). Genetic variation will include germline and somatic variation. Core A will provide informatics and statistics support for these experiments. Core A personnel have expertise in bioinformatics, systems biology, statistics, process management, and high performance computing. Dr. Bond has worked with the P01 since its inception. Aim 1 (Informatics) Identify variants for functional studies. A central role of Core A is to support identification of variants, for experimental studies, that are expected to have consequences for protein function. These variants are identified using DNA sequences available from large- scale sequence projects such as the 1000 Genomes Project and The Cancer Genome Atlas. Core A annotates the variants using publicly available software. Core A (Drs. Bond and Dragon) host weekly meetings at which these variants are presented and discussed. These meetings provide consistent communications with members of the four projects. Aim 2 (Statistics) Provide software and statistical support for hypothesis tests. The laboratory studies proposed in Projects 1-4 will characterize the consequences of this variation for protein structure, interactions, damage search and catalysis as well as cellular proliferation and survival. Core A statistical services will support design and analysis of these experiments.